2. Academic Validation
  3. Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics

Spatial transcriptomic analysis drives PET imaging of tight junction protein expression in pancreatic cancer theranostics

  • Nat Commun. 2024 Dec 30;15(1):10751. doi: 10.1038/s41467-024-54761-6.
James Wang # 1,  Jai Woong Seo # 1,  Aris J Kare # 1 2,  Martin Schneider 1,  Mallesh Pandrala 1,  Spencer K Tumbale 1,  Marina N Raie 1,  Gokce Engudar 1,  Nisi Zhang 1,  Yutong Guo 1,  Xiaoxu Zhong 3,  Sofia Ferreira 3,  Bo Wu 1,  Laura D Attardi 3 4,  Guillem Pratx 3,  Andrei Iagaru 5,  Ryan L Brunsing 6,  Gregory W Charville 7,  Walter G Park 8,  Katherine W Ferrara 9
Affiliations

Affiliations

  • 1 Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
  • 2 Department of Bioengineering, Stanford University, 443 Via Ortega, Stanford, CA, USA.
  • 3 Department of Radiation Oncology, Stanford University, 857 Blake Wilbur Drive, Stanford, CA, USA.
  • 4 Department of Genetics, Stanford University, 291 Campus Drive, Stanford, CA, USA.
  • 5 Nuclear Medicine and Molecular Imaging Division, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
  • 6 Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
  • 7 Department of Pathology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
  • 8 Department of Medicine-Gastroenterology & Hepatology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA.
  • 9 Molecular Imaging Program at Stanford, Department of Radiology, Stanford University, 300 Pasteur Drive, Stanford, CA, USA. kwferrar@stanford.edu.
  • # Contributed equally.
PMID: 39737976 DOI: 10.1038/s41467-024-54761-6
Abstract

Molecular imaging using positron emission tomography (PET) provides sensitive detection and mapping of molecular targets. While cancer-associated fibroblasts and integrins have been proposed as targets for imaging of pancreatic ductal adenocarcinoma (PDAC), herein, spatial transcriptomics and proteomics of human surgical samples are applied to select PDAC targets. We find that selected Cancer cell surface markers are spatially correlated and provide specific Cancer localization, whereas the spatial correlation between Cancer markers and immune-related or fibroblast markers is low. Claudin-4 expression increases ~16 fold in Cancer as compared with normal pancreas, and tight junction localization confers low background for imaging in normal tissue. We develop a peptide-based molecular imaging agent targeted to claudin-4 with accumulation to ~25% injected activity per cubic centimeter (IA/cc) in metastases and ~18% IA/cc in tumors. Our work motivates a data-driven approach to selection of molecular targets.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P11785
    Claudin-4结合剂
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